title: Irreversible immunoexpression of matrix metalloproteinase-9 in proximal tubular epithelium of renal allografts with acute rejection.
abstract: BACKGROUND
  Matrix metalloproteinase-9 (MMP-9) is the most important member of the MMP family responsible for the development and progression of various renal diseases. Our study aims to investigate the localization of MMP-9 in human renal allografts and to assess whether MMP-9 immunostaining is contributory to detect pathological change in renal biopsy.
  
  
  METHODS
  We examined 150 renal allograft biopsies (48 baseline and 102 follow-up) from 49 transplants and analyzed the associations of clinical and histopathological data with the MMP-9 staining intensity using a semi-quantitative scoring.
  
  
  RESULTS
  MMP-9 immunostaining in proximal tubule epithelium was negative before transplantation, but positive in biopsies with episodes, particularly with acute cellular rejection (ACR) and acute calcineurin inhibitor (CNI) toxicity. Tubulitis was the most significant association factor (p < 0.0001) with increased MMP-9 staining intensity. The expression in proximal tubules remained augmented in allografts recovered from ACR episodes, while it was disappeared or diminished in those recovered from acute CNI toxicity or ischemia/reperfusion effects.
  
  
  CONCLUSIONS
  These findings suggest the necessary participation of MMP-9 in the pathogenesis of tubulitis and the subsequent stage of pathogenesis in ACR. Up-regulation of MMP-9 expression in the proximal tubule could be a new indicator of tubular injury and a predictive factor for the prognosis of renal allograft.
authors.affiliation: Department of Urology, St. Marianna University School of Medicine, Kawasaki, Japan. k2kitajima@marianna-u.ac.jp
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kitajima
authors.forename: Junki
authors.initials: J
authors.lastname: Koike
authors.forename: Shiari
authors.initials: S
authors.lastname: Nozawa
authors.forename: Miki
authors.initials: M
authors.lastname: Yoshiike
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takagi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Chikaraishi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003131:Combined Modality Therapy; D005260:Female; D006084:Graft Rejection / Q000201:enzymology* / Q000517:prevention & control*; D006801:Humans; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D007683:Kidney Tubular Necrosis, Acute / Q000201:enzymology* / Q000628:therapy; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000276:immunology* / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D020780:Matrix Metalloproteinase 9